11181547

pubmed:Citation

3

Receptor activator of nuclear factor-kappa B ligand [RANK ligand (RANK-L)] stimulates mature osteoclasts to resorb bone, a process associated with NF-kappa B activation. RANK-L also prompts macrophages to develop the osteoclast phenotype. Although NF-kappa B is essential for osteoclast differentiation, it is not known whether RANK-L activates this transcription complex in osteoclast precursors. We report that RANK-L rapidly induces NF-kappa B activation in both authentic osteoclast precursors, namely bone marrow macrophages, and RAW 264.7 cells, a murine macrophage line also capable of RANK-L-mediated osteoclastogenesis. Supershift studies reveal the RANK-L-induced DNA binding moiety contains p50/p65, the most common NF-kappa B complex. Subcellular translocation of p50 and p65 subunits is confirmed by Western blots and immunofluorescence analysis. RANK-L activates NF-kappa B in both bone marrow macrophages and RAW 264.7 cells by serine phosphorylation of I kappa B alpha within 5 min, resulting in rapid I kappa B alpha degradation and resynthesis. Attesting to function, RANK-L treatment of RAW 264.7 cells transiently transfected with a plasmid containing NF-kappa B consensus elements linked to luciferase greatly enhances reporter activity. Our data suggest that activation of the NF-kappa B pathway is an integral component of RANK-L-induced osteoclast differentiation.

eng

AIM

MEDLINE

0013-7227

Print

NLM

1290-5

pubmed-meshheading:11181547-Animals, pubmed-meshheading:11181547-Biological Transport, pubmed-meshheading:11181547-Carrier Proteins, pubmed-meshheading:11181547-Cell Nucleus, pubmed-meshheading:11181547-Cells, Cultured, pubmed-meshheading:11181547-Dimerization, pubmed-meshheading:11181547-Genes, Reporter, pubmed-meshheading:11181547-I-kappa B Proteins, pubmed-meshheading:11181547-Male, pubmed-meshheading:11181547-Membrane Glycoproteins, pubmed-meshheading:11181547-Mice, pubmed-meshheading:11181547-Mice, Inbred C3H, pubmed-meshheading:11181547-NF-kappa B, pubmed-meshheading:11181547-Osteoclasts, pubmed-meshheading:11181547-Phosphorylation, pubmed-meshheading:11181547-RANK Ligand, pubmed-meshheading:11181547-Receptor Activator of Nuclear Factor-kappa B, pubmed-meshheading:11181547-Serine, pubmed-meshheading:11181547-Stem Cells

Receptor activator of nuclear factor-kappa b ligand activates nuclear factor-kappa b in osteoclast precursors.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't